Tier 4 — mechanistic

Alpha-ketoglutarate Potentiates IL-1β Production and Suppressive Mechanisms of Myeloid-Derived Suppressor Cells by Altering Redox Metabolism and Inducing Autophagy

Milanović M, Pavlović L, Bekić M, Đokić J, Stojadinović M, Radojević D, Čolić M, Tomić S
International Journal of Biological Sciences 2026 22(10):5119-5141

Bibliography

PubMed
PMID 42212338
PubMed Central
PMC13215254
DOI
10.7150/ijbs.127309
Funding
Academic research funding is reported in the open-access article.
Competing interests
The authors declared that no competing interest exists.

Study snapshot

DesignMechanistic human monocyte-derived myeloid-suppressor-cell study.
ModelHuman monocyte-derived MDSCs and T-cell co-cultures.
SampleMultiple independent human donor experiments.
InterventionNon-esterified AKG during MDSC differentiation; OXGR1 and autophagy pathways manipulated experimentally.
DurationMulti-day differentiation and co-culture protocols.
EndpointsMDSC expansion; IL-1β; IL-10; Th17 responses; Regulatory T cells; Autophagy flux; OXGR1/ROS signaling

What the study showed, in plain terms

This 2026 paper adds a critical counterweight to blanket claims that AKG simply lowers inflammation.

In a human myeloid-derived suppressor-cell model, non-esterified AKG enhanced immunosuppressive functions but also increased IL-1β production and Th17 expansion through OXGR1/ROS-linked signaling.

The authors concluded that AKG could, in this tumor-immunology context, promote chronic inflammation and T-cell dysregulation. This is mechanistic cell evidence, not an oral-supplement outcome.

Key findings

  • AKG expanded a suppressive MDSC phenotype and increased IL-10-related regulatory activity.
  • AKG increased IL-1β and Th17-promoting activity after stimulation.
  • OXGR1/ROS and Atg5-dependent autophagy mediated different components of the response.

What this study can and cannot tell us

  • Human cells studied outside the body.
  • High culture concentrations should not be interpreted as achievable oral Ca-AKG exposure.
  • Tumor-microenvironment immunology may differ from healthy systemic inflammation.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology